Pathological conditions (hereinafter may be referred to simply as diseases) such as diabetic gastroparesis, postoperative gastroparesis, and functional dyspepsia are known to show suppressed postprandial gastric motility and significantly degraded ability in gastric emptying of food. As drugs for enhancing gastric emptying of food to cope with such conditions, itopride hydrochloride and mosapride citrate, for example, are known. However, whether these drugs can provide sufficient effect on patients with severe conditions is still unknown. Accordingly, development of a truly effective drug is demanded.
Ghrelin is a peptide found in the stomach, and predominantly produced by gastric endocrine cells. Ghrelin is known as an appetite-stimulating peptide related to enhanced appetite and an increase in body weight. Regarding the gastric emptying of food by ghrelin, a report describes that continuous intravenous administration of ghrelin or massive administration of ghrelin to healthy subjects and patients with diabetes, both after food intake, accelerates gastric emptying (Non-Patent Documents 1 and 2). Also, administration of TZP-102, a ghrelin agonist, to fasting subjects does not accelerate gastric emptying (Non-Patent Document 3).
Motilin is a peptide of 22 amino acid residues, and is known as a substance that causes interdigestive gastric contractions in conscious dogs and humans. Motilin, when continuously administered intravenously to fasting subjects, is known to accelerate gastric emptying (Non-Patent Document 4). There is also a report describing that administration of mitemcinal, a motilin agonist, to fasting subjects enhances gastric emptying (Non-Patent Document 5).
Recently, an in vitro study was performed to investigate the gastric contractions inducing mechanism of ghrelin using an isolated stomach of Suncus murinus. The study revealed that administration of ghrelin alone, even at a high dose, does not accelerate gastric contractions, but treatment of subjects with a low dose of motilin in advance recovers susceptibility of ghrelin, suggesting that prior administration of motilin may open the gate of ghrelin circuit (Non-Patent Document 6).